Efeitos do potencial probiótico Enterococcus faecium 32 e de sua associação com o extrato da alga marinha Caulerpa mexicana no tratamento de colite experimental murina

Ulcerative colitis comprising an inflammatory bowel disease, whose most severe consequence is the development of intestinal neoplasia. The drugs currently used to treat the disease trigger a variety of serious adverse effects and are not effective in many cases. Recent studies demonstrated the effectiveness of natural products for the treatment of inflammatory processes. Seaweed extracts and their purified products have shown protective effects in models of inflammation and the association of traditional therapies with probiotics has significantly improved the clinical symptoms of ulcerative colitis. Therefore, the aims of this study include evaluating the potential effects of the use of probiotic strain Enterococcus faecium 32 (Ef32), the methanolic extract of the green seaweed Caulerpa mexicana (M.E.) and their concomitant administration in a murine model of colitis induced by dextran sodium sulfate (DSS). Accordingly, C57BL /6 mice were pretreated orally with Ef32 (109 CFU/ml) for seven days. In the seven days following, the colitis was induced by administration of 3% DSS (w/v) diluted in the animals drinking water. During this period, animals were treated daily with Ef32 and the M.E. (2.0 mg/kg) every other day by intravenous route. The development of colitis was monitored by the disease activity index (DAI), which takes into account the loss of body weight, consistency and presence of blood in stools. After euthanasia, the colon was removed, its length measured and tissue samples were destined for histological analysis and culture for cytokine quantification. The levels of cytokines in the culture supernatant of the colon were measured by ELISA. The treatments with the probiotic Ef32 or the M.E. alone or the combination of these two substances provoked significant improvement as to weight loss and DAI, and prevented the shortening of the colon in response to DSS. The isolated treatments triggered a slight improvement in intestinal mucosal tissue damage. However, their combination was able to completely repair the injury triggered by DSS. The association was also able to reduce the levels of all the cytokines analyzed (IFN-γ, IL-4, IL-6, IL-12, IL-17A and TNF-α). On the other hand, the treatment with Ef32 did not interfere with the levels of TNF-α, whereas treatment with M.E. did not alter the levels of IL-6. Moreover, the treatment with Ef32 not interferes in TNF-α levels, whereas treatment with M.E. did not alter the levels of IL-6. Therefore, the potential probiotic Ef32 and M.E. and especially when these samples were associated proved promising alternatives in the treatment of ulcerative colitis as demonstrated in an experimental model because of its beneficial effects on morphological and clinical parameters, and by reducing the production of proinflammatory cytokines of Th1, Th2 and Th17

Análise comparativa da imunoexpressão das proteínas hmlh1 e hmsh2 em carcinomas epidermóides de lábio inferior e queilites actínicas com graus variados de displasia

Lip squamous cell carcinoma (SCC) may develop from a premalignant condition, actinic cheilitis (AC) in 95% of the cases. Both premalignant and neoplastic lip diseases are caused mainly by chronic exposure to the ultraviolet component of solar radiation, especially UVB. This exposure causes disruption of the cell cycle and damage to DNA repair systems, like mismatch repair, altering proteins repair as hMLH1 and hMSH2. This research aimed to investigate the immunohistochemical expression of hMLH1 and hMSH2 proteins in lower lip SCCs and ACs, providing additional information about carcinogenesis of the lower lip. The sample consisted 40 cases of ACs and 40 cases of lower lip SCCs. Histological sections of 3 μm were submitted to immunoperoxidase method, for immunohistochemical analysis of lesions were counted in 1000 cells (positive and negative), data were evaluated both in absolute numbers and percentage of immunostained cells, the latter by assigning scores. Associations of the variables and comparative analysis of biomarker expression were performed by Fisher s exact and Pearson s chi-square, "t" student, one-way ANOVA, Mann- Whitney e Kruskal-Wallis tests. The level of significance was 5%. It was found that, in lower lip SCC, the mean of the proteins was higher in female patients (hMLH1= 369,80 + 223,98; hMHS2 = 534,80 + 343,62), less than 50 years old (hMLH1 = 285,50 + 190,65; hMHS2 = 540,00 + 274,79) and classified as low-grade malignancy (hMLH1 = 264,59 + 179,21; hMHS2 = 519,32 + 302,58), in these data only to sex, for hMLH1 protein, was statistically significant (p=0.034). Comparing the different lesions, we observed that for both hMLH1 and hMSH2 protein, the average of positive epithelial cells decreased as the lesion was graded at later stages. The ACs classified without dysplasia or mild dysplasia had the highest average of immunostained cells (hMLH1 = 721.23 + 88.116; hMHS2 = 781.50 + 156.93). The ACs classified as moderate or severe dysplasia had intermediate values (hMLH1 = 532,86 + 197,72; hMHS2 = 611,14 + 172,48) and SSCs of the lower lip had the lowest averages (hMLH1 = 255,03 + 199,47; hMHS2 = 518,38 + 265,68). There was a statistically significant difference between groups (p<0.001). In conclusion, our data support the hypothesis that changes in immunoexpression of these proteins is related to the process of carcinogenesis of the lower lip